HyperlipidemiaPhase 3GAUSS-2NCT01763905

Goal Achievement After Utilizing an Anti-PCSK9 Antibody in Statin Intolerant Subjects -2

A Phase 3 study testing Evolocumab and Ezetimibe in people with Hyperlipidemia, run by Amgen at 58 sites in 14 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

The primary objective was to evaluate the effect of 12 weeks of subcutaneous (SC) evolocumab every 2 weeks (Q2W) and monthly (QM), compared with ezetimibe, on percent change from baseline in low-density lipoprotein cholesterol (LDL-C) in hypercholesterolemic adults unable to tolerate an effective dose of a statin… Read more about this study

Who is it for?: Ages 18 to 80 years
Conditions the study is for: Hyperlipidemia
What is being tested?: Evolocumab and Ezetimibe
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 307 participants
Where: 58 sitesin 14 countries
Study dates: 24 Jan 2013to 19 Nov 2013
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 80 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Male or female ≥ 18 to ≤ 80 years of age
Not on a statin or on a low dose statin with stable dose for at least 4 weeks
History of intolerance to at least 2 statins
Subject not at LDL-C goal
Lipid lowering therapy has been stable prior to enrolment for at least 4 weeks.
Fasting triglycerides ≤ 400 mg/dL

Who cannot join

New York Heart Association (NYHA) III or IV heart failure
Uncontrolled cardiac arrhythmia
Uncontrolled hypertension
Type 1 diabetes, poorly controlled type 2 diabetes
Uncontrolled hypothyroidism or hyperthyroidism

Trial locations and contacts

58 sites in 14 countries.

Country

City, postcode or hospital

58 sites in 14 countries

United States20 sites

Research Site
Akron, Ohio, 44311
Research Site
Atlanta, Georgia, 30338
Research Site
Atlanta, Georgia, 30342
Research Site
Auburn, Maine, 04210
Research Site
Carmichael, California, 95608
Research Site
Cincinnati, Ohio, 45212
Research Site
Cleveland, Ohio, 44195
Research Site
Henderson, Nevada, 89052
Research Site
Houston, Texas, 77030
Research Site
Las Vegas, Nevada, 89117
Research Site
Las Vegas, Nevada, 89148
Research Site
Los Angeles, California, 90048
Research Site
Mission Viejo, California, 92691
Research Site
New York, New York, 10029
Research Site
Norman, Oklahoma, 73069
Research Site
Raleigh, North Carolina, 27609
Research Site
Savannah, Georgia, 31406
Research Site
St Louis, Missouri, 63110
Research Site
Thousand Oaks, California, 91360
Research Site
Traverse City, Michigan, 49684

Other trials in United States

Australia4 sites

Research Site
Camperdown, New South Wales, 2015
Research Site
Melbourne, Victoria, 3004
Research Site
Milton, Queensland, 4064
Research Site
Perth, Western Australia, 6000

Other trials in Australia

United Kingdom4 sites

Research Site
Liverpool, L22 0LG
Research Site
London, NW3 2QG
Research Site
Telford, TF1 6TF
Research Site
West Bromwich, B71 4HJ

Other trials in United Kingdom

Belgium3 sites

Research Site
Brussels, 1200
Research Site
Ghent, 9000
Research Site
La Louvière, 7100

Other trials in Belgium

Canada3 sites

Research Site
Lachine, Quebec, H8S 2E4
Research Site
Newmarket, Ontario, L3Y 5G8
Research Site
Pointe-Claire, Quebec, H9R 3J1

Other trials in Canada

Denmark3 sites

Research Site
Aalborg, 9000
Research Site
Ballerup Municipality, 2750
Research Site
Vejle, 7100

Other trials in Denmark

France3 sites

Research Site
Lille, 59037
Research Site
Paris, 75651
Research Site
Vénissieux, 69200

Other trials in France

Germany3 sites

Research Site
Bad Krozingen, 79189
Research Site
Dresden, 01307
Research Site
Heppenheim an der Bergstrasse, 64646

Other trials in Germany

Netherlands3 sites

Research Site
Alkmaar, 1815 JD
Research Site
Amsterdam, 1105 AZ
Research Site
Groningen, 9713 GZ

Other trials in Netherlands

South Africa3 sites

Research Site
Midrand, Gauteng, 1685
Research Site
Observatory, Western Cape, 7925
Research Site
Somerset West, Western Cape, 7130

Other trials in South Africa

Spain3 sites

Research Site
Córdoba, Andalusia, 14004
Research Site
Reus, Catalonia, 43204
Research Site
Zaragoza, Aragon, 50009

Other trials in Spain

Hong Kong2 sites

Research Site
Hong Kong
Research Site
New Territories

Other trials in Hong Kong

Poland2 sites

Research Site
Lodz, 90-368
Research Site
Warsaw, 04-730

Other trials in Poland

Switzerland2 sites

Research Site
Lugano, 6900
Research Site
Reinach, 4153

Other trials in Switzerland

About this study

Official title: A Double-blind, Randomized, Multicenter Study to Evaluate Safety and Efficacy of AMG 145, Compared With Ezetimibe, in Hypercholesterolemic Subjects Unable to Tolerate an Effective Dose of a HMG-CoA Reductase Inhibitor

Conditions: Hyperlipidemia
Being tested: Evolocumab, Placebo to Evolocumab, Ezetimibe, Placebo to Ezetimibe
Keywords: High Cholesterol, Treatment for high cholesterol, Lowering cholesterol, Lowering high cholesterol, Hypercholesterolemia
Medical subject headings: Hyperlipidemias, Hypercholesterolemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

EvolocumabBiological
Also called AMG 145, Repatha
Subcutaneous injection
Placebo to EvolocumabDrug
Subcutaneous injection
EzetimibeDrug
Also called Zetia
Tablet for oral administration
Placebo to EzetimibeDrug
Tablet for oral administration

Study groups in NCT01763905
Study group	Role	What they receive
Ezetimibe (Q2W)	Active comparator	Participants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks. Receives: Drug: Placebo to Evolocumab; Drug: Ezetimibe
Ezetimibe (QM)	Active comparator	Participants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks. Receives: Drug: Placebo to Evolocumab; Drug: Ezetimibe
Evolocumab Q2W	Experimental	Participants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks. Receives: Biological: Evolocumab; Drug: Placebo to Ezetimibe
Evolocumab QM	Experimental	Participants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks. Receives: Biological: Evolocumab; Drug: Placebo to Ezetimibe

What is being measured

The primary outcome is the main question the study is designed to answer.

Percent Change From Baseline in LDL-C at Week 12
Measured: Baseline and Week 12
Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12
Measured: Baseline and Weeks 10 and 12

Secondary outcomes (20)

Change From Baseline in LDL-C at the Mean of Weeks 10 and 12
Measured: Baseline and Weeks 10 and 12
Change From Baseline in LDL-C at Week 12
Measured: Baseline and Week 12
Percentage of Participants With Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL (1.8 mmol/L)
Measured: Weeks 10 and 12
Percentage of Participants With LDL-C < 70 mg/dL (1.8 mmol/L) at Week 12
Measured: Week 12
Percent Change From Baseline in Non-HDL-C at the Mean of Weeks 10 and 12
Measured: Baseline and Weeks 10 and 12
Percent Change From Baseline in Non-HDL-C at Week 12
Measured: Baseline and Week 12
Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12
Measured: Baseline and Weeks 10 and 12
Percent Change From Baseline in Apolipoprotein B at Week 12
Measured: Baseline and Week 12
Percent Change From Baseline in the Total Cholesterol/High Density Lipoprotein Cholesterol Ratio at the Mean of Weeks 10 and 12
Measured: Baseline and Weeks 10 and 12
Percent Change From Baseline in the Total Cholesterol/High Density Lipoprotein Cholesterol Ratio at Week 12
Measured: Baseline and Week 12
Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at the Mean of Weeks 10 and 12
Measured: Baseline and Weeks 10 and 12
Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12
Measured: Baseline and Week 12
Percent Change From Baseline in Lipoprotein (a) at the Mean of Weeks 10 and 12
Measured: Baseline and Weeks 10 and 12
Percent Change From Baseline in Lipoprotein (a) at Week 12
Measured: Baseline and Week 12
Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12
Measured: Baseline and Weeks 10 and 12
Percent Change From Baseline in Triglycerides at Week 12
Measured: Baseline and Week 12
Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at the Mean of Weeks 10 and 12
Measured: Baseline and Weeks 10 and 12
Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Week 12
Measured: Baseline and Week 12
Percent Change From Baseline in Very Low-Density Lipoprotein Cholesterol at the Mean of Weeks 10 and 12
Measured: Baseline and Weeks 10 and 12
Percent Change From Baseline in Very Low-Density Lipoprotein Cholesterol at Week 12
Measured: Baseline and Week 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

24 Jan 201319 Nov 2013

First posted9 Jan 2013 (estimated)
Study start24 Jan 2013
Primary completion19 Nov 2013
Study completion19 Nov 2013

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (11)Papers the sponsor has linked to this study.
Other trials for HyperlipidemiaStudies of the same condition, open and under way.
More trials run by AmgenThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 307 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01763905
Sponsor's protocol ID: 20110116
Other IDs: 2012-001364-30
Acronym: GAUSS-2
Status last verified: Jul 2020
First submitted: 7 Jan 2013
Last updated: 20 Jul 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Toth PP, Descamps O, Genest J, Sattar N, Preiss D, Dent R, Djedjos C, Wu Y, Geller M, Uhart M, Somaratne R, Wasserman SM; PROFICIO Investigators. Pooled Safety Analysis of Evolocumab in Over 6000 Patients From Double-Blind and Open-Label Extension Studies. Circulation. 2017 May 9;135(19):1819-1831. doi: 10.1161/CIRCULATIONAHA.116.025233. Epub 2017 Mar 1.
PubMed 28249876
Kuchimanchi M, Grover A, Emery MG, Somaratne R, Wasserman SM, Gibbs JP, Doshi S. Population pharmacokinetics and exposure-response modeling and simulation for evolocumab in healthy volunteers and patients with hypercholesterolemia. J Pharmacokinet Pharmacodyn. 2018 Jun;45(3):505-522. doi: 10.1007/s10928-018-9592-y. Epub 2018 May 7.
PubMed 29736889
Cho L, Dent R, Stroes ESG, Stein EA, Sullivan D, Ruzza A, Flower A, Somaratne R, Rosenson RS. Persistent Safety and Efficacy of Evolocumab in Patients with Statin Intolerance: a Subset Analysis of the OSLER Open-Label Extension Studies. Cardiovasc Drugs Ther. 2018 Aug;32(4):365-372. doi: 10.1007/s10557-018-6817-7.
PubMed 30073585
Kasichayanula S, Grover A, Emery MG, Gibbs MA, Somaratne R, Wasserman SM, Gibbs JP. Clinical Pharmacokinetics and Pharmacodynamics of Evolocumab, a PCSK9 Inhibitor. Clin Pharmacokinet. 2018 Jul;57(7):769-779. doi: 10.1007/s40262-017-0620-7.
PubMed 29353350
Wasserman SM, Sabatine MS, Koren MJ, Giugliano RP, Legg JC, Emery MG, Doshi S, Liu T, Somaratne R, Gibbs JP. Comparison of LDL-C Reduction Using Different Evolocumab Doses and Intervals: Biological Insights and Treatment Implications. J Cardiovasc Pharmacol Ther. 2018 Sep;23(5):423-432. doi: 10.1177/1074248418774043. Epub 2018 May 16.
PubMed 29768954
Cho L, Rocco M, Colquhoun D, Sullivan D, Rosenson RS, Dent R, Xue A, Scott R, Wasserman SM, Stroes E. Design and rationale of the GAUSS-2 study trial: a double-blind, ezetimibe-controlled phase 3 study of the efficacy and tolerability of evolocumab (AMG 145) in subjects with hypercholesterolemia who are intolerant of statin therapy. Clin Cardiol. 2014 Mar;37(3):131-9. doi: 10.1002/clc.22248. Epub 2014 Jan 29.
PubMed 24477778
Stroes E, Colquhoun D, Sullivan D, Civeira F, Rosenson RS, Watts GF, Bruckert E, Cho L, Dent R, Knusel B, Xue A, Scott R, Wasserman SM, Rocco M; GAUSS-2 Investigators. Anti-PCSK9 antibody effectively lowers cholesterol in patients with statin intolerance: the GAUSS-2 randomized, placebo-controlled phase 3 clinical trial of evolocumab. J Am Coll Cardiol. 2014 Jun 17;63(23):2541-2548. doi: 10.1016/j.jacc.2014.03.019. Epub 2014 Mar 30.
PubMed 24694531
Shapiro MD, Minnier J, Tavori H, Kassahun H, Flower A, Somaratne R, Fazio S. Relationship Between Low-Density Lipoprotein Cholesterol and Lipoprotein(a) Lowering in Response to PCSK9 Inhibition With Evolocumab. J Am Heart Assoc. 2019 Feb 19;8(4):e010932. doi: 10.1161/JAHA.118.010932.
PubMed 30755061
Stroes E, Robinson JG, Raal FJ, Dufour R, Sullivan D, Kassahun H, Ma Y, Wasserman SM, Koren MJ. Consistent LDL-C response with evolocumab among patient subgroups in PROFICIO: A pooled analysis of 3146 patients from phase 3 studies. Clin Cardiol. 2018 Oct;41(10):1328-1335. doi: 10.1002/clc.23049. Epub 2018 Oct 21.
PubMed 30120772
Toth PP, Jones SR, Monsalvo ML, Elliott-Davey M, Lopez JAG, Banach M. Effect of Evolocumab on Non-High-Density Lipoprotein Cholesterol, Apolipoprotein B, and Lipoprotein(a): A Pooled Analysis of Phase 2 and Phase 3 Studies. J Am Heart Assoc. 2020 Mar 3;9(5):e014129. doi: 10.1161/JAHA.119.014129. Epub 2020 Mar 2.
PubMed 32114889
Koren MJ, Jones PH, Robinson JG, Sullivan D, Cho L, Hucko T, Lopez JAG, Fleishman AN, Somaratne R, Stroes E. A Comparison of Ezetimibe and Evolocumab for Atherogenic Lipid Reduction in Four Patient Populations: A Pooled Efficacy and Safety Analysis of Three Phase 3 Studies. Cardiol Ther. 2020 Dec;9(2):447-465. doi: 10.1007/s40119-020-00181-8. Epub 2020 Jun 20.
PubMed 32564340

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Not yet recruiting
Plasma Lipids-Dependent Vitamin E Metabolism During Dynamic Hyperlipidemia
Lipid Metabolism Disorders
Active, not recruiting
Developing a Learning COmmunity to Increase eNgagemeNt and Enrollment in Cardiovascular Clinical Trials (CONNECT)
Cardiovascular Diseases, Hypertension
Active, not recruitingPhase 3
A Study of Inclisiran to Prevent Cardiovascular Events in High-risk Primary Prevention Patients.
Primary Prevention of Atherosclerotic Cardiovascular Disease
RecruitingObservational study
Causes and Natural History of Dyslipidemias
Hypercholesterolemia, Atherosclerosis
Active, not recruitingObservational study
Early Detection of Familial Hypercholesterolaemia in Pre-school Children ( CzeCH-IT)
Familial Hypercholesterolaemia

All Hyperlipidemia trials

Study at a glance

From the registry record, last updated by the sponsor on 20 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Double-blind, Randomized, Multicenter Study to Evaluate Safety and Efficacy of AMG 145, Compared With Ezetimibe, in Hypercholesterolemic Subjects Unable to Tolerate an Effective Dose of a HMG-CoA Reductase Inhibitor
ClinicalTrials.gov ID: NCT01763905
Acronym / sponsor ID: GAUSS-2 / 20110116
Conditions: Hyperlipidemia
Keywords: High Cholesterol, Treatment for high cholesterol, Lowering cholesterol, Lowering high cholesterol, Hypercholesterolemia
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 307 participants (actual)
Lead sponsor: AmgenIndustry (pharma, biotech, devices)
Study start: 24 Jan 2013 (actual)
Primary completion: 19 Nov 2013 (actual)
Study completion: 19 Nov 2013 (actual)
First posted: 9 Jan 2013 (estimated)
Results: Posted 22 Dec 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 4

Arm	Type	Receives
Ezetimibe (Q2W)	Active comparator	Drug: Placebo to Evolocumab, Drug: EzetimibeParticipants received placebo subcutaneous injection once every 2 weeks and 10 mg ezetimibe orally once a day for up to 12 weeks.
Ezetimibe (QM)	Active comparator	Drug: Placebo to Evolocumab, Drug: EzetimibeParticipants received placebo subcutaneous injection once a month and 10 mg ezetimibe orally once a day for up to 12 weeks.
Evolocumab Q2W	Experimental	Biological: Evolocumab, Drug: Placebo to EzetimibeParticipants received 140 mg evolocumab by subcutaneous injection once every 2 weeks and placebo tablets once a day for up to 12 weeks.
Evolocumab QM	Experimental	Biological: Evolocumab, Drug: Placebo to EzetimibeParticipants received 420 mg evolocumab by subcutaneous injection once a month and placebo tablets once a day for up to 12 weeks.

Who may qualify

Ages: 18 to 80 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

Male or female ≥ 18 to ≤ 80 years of age
Not on a statin or on a low dose statin with stable dose for at least 4 weeks
History of intolerance to at least 2 statins
Subject not at LDL-C goal
Lipid lowering therapy has been stable prior to enrolment for at least 4 weeks.

Key exclusion criteria (5 listed)

New York Heart Association (NYHA) III or IV heart failure
Uncontrolled cardiac arrhythmia
Uncontrolled hypertension
Type 1 diabetes, poorly controlled type 2 diabetes
Uncontrolled hypothyroidism or hyperthyroidism

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
EvolocumabAlso: AMG 145, RepathaSubcutaneous injection	Biological	Evolocumab Q2W, Evolocumab QM
Placebo to EvolocumabSubcutaneous injection	Drug	Ezetimibe (Q2W), Ezetimibe (QM)
EzetimibeAlso: ZetiaTablet for oral administration	Drug	Ezetimibe (Q2W), Ezetimibe (QM)
Placebo to EzetimibeTablet for oral administration	Drug	Evolocumab Q2W, Evolocumab QM

Primary outcome

Percent Change From Baseline in LDL-C at Week 12
Time frame: Baseline and Week 12
Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12
Time frame: Baseline and Weeks 10 and 12

20 secondary outcomes

Change From Baseline in LDL-C at the Mean of Weeks 10 and 12
Time frame: Baseline and Weeks 10 and 12
Change From Baseline in LDL-C at Week 12
Time frame: Baseline and Week 12
Percentage of Participants With Mean LDL-C at Weeks 10 and 12 of Less Than 70 mg/dL (1.8 mmol/L)
Time frame: Weeks 10 and 12
Percentage of Participants With LDL-C < 70 mg/dL (1.8 mmol/L) at Week 12
Time frame: Week 12
Percent Change From Baseline in Non-HDL-C at the Mean of Weeks 10 and 12
Time frame: Baseline and Weeks 10 and 12
Percent Change From Baseline in Non-HDL-C at Week 12
Time frame: Baseline and Week 12
Percent Change From Baseline in Apolipoprotein B at the Mean of Weeks 10 and 12
Time frame: Baseline and Weeks 10 and 12
Percent Change From Baseline in Apolipoprotein B at Week 12
Time frame: Baseline and Week 12
Percent Change From Baseline in the Total Cholesterol/High Density Lipoprotein Cholesterol Ratio at the Mean of Weeks 10 and 12
Time frame: Baseline and Weeks 10 and 12
Percent Change From Baseline in the Total Cholesterol/High Density Lipoprotein Cholesterol Ratio at Week 12
Time frame: Baseline and Week 12
Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at the Mean of Weeks 10 and 12
Time frame: Baseline and Weeks 10 and 12
Percent Change From Baseline in Apolipoprotein B/Apolipoprotein A1 Ratio at Week 12
Time frame: Baseline and Week 12
Percent Change From Baseline in Lipoprotein (a) at the Mean of Weeks 10 and 12
Time frame: Baseline and Weeks 10 and 12
Percent Change From Baseline in Lipoprotein (a) at Week 12
Time frame: Baseline and Week 12
Percent Change From Baseline in Triglycerides at the Mean of Weeks 10 and 12
Time frame: Baseline and Weeks 10 and 12
Percent Change From Baseline in Triglycerides at Week 12
Time frame: Baseline and Week 12
Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at the Mean of Weeks 10 and 12
Time frame: Baseline and Weeks 10 and 12
Percent Change From Baseline in High-Density Lipoprotein Cholesterol (HDL-C) at Week 12
Time frame: Baseline and Week 12
Percent Change From Baseline in Very Low-Density Lipoprotein Cholesterol at the Mean of Weeks 10 and 12
Time frame: Baseline and Weeks 10 and 12
Percent Change From Baseline in Very Low-Density Lipoprotein Cholesterol at Week 12
Time frame: Baseline and Week 12

Results and safety

Results posted to the registry on 22 Dec 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Ezetimibe (Q2W)	51	45
Ezetimibe (QM)	51	50
Evolocumab Q2W	103	94
Evolocumab QM	102	101

Primary outcome: Percent Change From Baseline in LDL-C at Week 12

Time frame: Baseline and Week 12. Least squares mean (Standard Error). Unit: percent change

Measure	Ezetimibe (Q2W) n = 51	Ezetimibe (QM) n = 51	Evolocumab Q2W n = 103	Evolocumab QM n = 102
Value	-18.08 (2.52)	-15.05 (2.13)	-56.14 (1.91)	-52.60 (1.58)

Ezetimibe (Q2W) vs Evolocumab Q2W: LS Mean Treatment Difference: -38.06 (95% CI -43.73 to -32.99), p <0.001, Repeated measures linear effects model
Ezetimibe (QM) vs Evolocumab QM: LS Mean Treatment Difference: -37.55 (95% CI -42.16 to -32.94), p <0.001, Repeated measures linear effects model

Population analysed: Full analysis set (all randomized participants who received at least 1 dose of investigational product (subcutaneously or orally)) with available data (no imputation was performed).

Primary outcome: Percent Change From Baseline in LDL-C at the Mean of Weeks 10 and 12

Time frame: Baseline and Weeks 10 and 12. Least squares mean (Standard Error). Unit: percent change

Measure	Ezetimibe (Q2W) n = 51	Ezetimibe (QM) n = 51	Evolocumab Q2W n = 103	Evolocumab QM n = 102
Value	-19.21 (2.40)	-16.62 (2.03)	-56.11 (1.83)	-55.31 (1.53)

Ezetimibe (Q2W) vs Evolocumab Q2W: LS Mean Treatment Difference: -36.90 (95% CI -42.26 to -31.55), p <0.001, Repeated measures linear effects model
Ezetimibe (QM) vs Evolocumab QM: LS Mean Treatment Difference: -38.69 (95% CI -43.06 to -34.22), p <0.001, Repeated measures linear effects model

Population analysed: Full analysis set with available data (no imputation was performed).

20 secondary outcomes are reported in the full results.

Adverse events

Time frame: From the first dose of blinded investigational product until the end of the study (up to 14 weeks).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Ezetimibe (Q2W)	1 of 51 (2%)	20 of 51 (39.2%)	Not reported
Ezetimibe (QM)	3 of 51 (5.9%)	29 of 51 (56.9%)	Not reported
Evolocumab Q2W	5 of 103 (4.9%)	28 of 103 (27.2%)	Not reported
Evolocumab QM	1 of 102 (1%)	42 of 102 (41.2%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 20 Jul 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 28249876Toth PP, Descamps O, Genest J, Sattar N, Preiss D, Dent R, Djedjos C, Wu Y, Geller M, Uhart M, Somaratne R, Wasserman SM; PROFICIO Investigators. Pooled Safety Analysis of Evolocumab in Over 6000 Patients From Double-Blind and Open-Label Extension Studies. Circulation. 2017 May 9;135(19):1819-1831. doi: 10.1161/CIRCULATIONAHA.116.025233. Epub 2017 Mar 1.
Background: PubMed 29736889Kuchimanchi M, Grover A, Emery MG, Somaratne R, Wasserman SM, Gibbs JP, Doshi S. Population pharmacokinetics and exposure-response modeling and simulation for evolocumab in healthy volunteers and patients with hypercholesterolemia. J Pharmacokinet Pharmacodyn. 2018 Jun;45(3):505-522. doi: 10.1007/s10928-018-9592-y. Epub 2018 May 7.
Background: PubMed 30073585Cho L, Dent R, Stroes ESG, Stein EA, Sullivan D, Ruzza A, Flower A, Somaratne R, Rosenson RS. Persistent Safety and Efficacy of Evolocumab in Patients with Statin Intolerance: a Subset Analysis of the OSLER Open-Label Extension Studies. Cardiovasc Drugs Ther. 2018 Aug;32(4):365-372. doi: 10.1007/s10557-018-6817-7.
Background: PubMed 29353350Kasichayanula S, Grover A, Emery MG, Gibbs MA, Somaratne R, Wasserman SM, Gibbs JP. Clinical Pharmacokinetics and Pharmacodynamics of Evolocumab, a PCSK9 Inhibitor. Clin Pharmacokinet. 2018 Jul;57(7):769-779. doi: 10.1007/s40262-017-0620-7.
Background: PubMed 29768954Wasserman SM, Sabatine MS, Koren MJ, Giugliano RP, Legg JC, Emery MG, Doshi S, Liu T, Somaratne R, Gibbs JP. Comparison of LDL-C Reduction Using Different Evolocumab Doses and Intervals: Biological Insights and Treatment Implications. J Cardiovasc Pharmacol Ther. 2018 Sep;23(5):423-432. doi: 10.1177/1074248418774043. Epub 2018 May 16.
Background: PubMed 24477778Cho L, Rocco M, Colquhoun D, Sullivan D, Rosenson RS, Dent R, Xue A, Scott R, Wasserman SM, Stroes E. Design and rationale of the GAUSS-2 study trial: a double-blind, ezetimibe-controlled phase 3 study of the efficacy and tolerability of evolocumab (AMG 145) in subjects with hypercholesterolemia who are intolerant of statin therapy. Clin Cardiol. 2014 Mar;37(3):131-9. doi: 10.1002/clc.22248. Epub 2014 Jan 29.
Background: PubMed 24694531Stroes E, Colquhoun D, Sullivan D, Civeira F, Rosenson RS, Watts GF, Bruckert E, Cho L, Dent R, Knusel B, Xue A, Scott R, Wasserman SM, Rocco M; GAUSS-2 Investigators. Anti-PCSK9 antibody effectively lowers cholesterol in patients with statin intolerance: the GAUSS-2 randomized, placebo-controlled phase 3 clinical trial of evolocumab. J Am Coll Cardiol. 2014 Jun 17;63(23):2541-2548. doi: 10.1016/j.jacc.2014.03.019. Epub 2014 Mar 30.
Background: PubMed 30755061Shapiro MD, Minnier J, Tavori H, Kassahun H, Flower A, Somaratne R, Fazio S. Relationship Between Low-Density Lipoprotein Cholesterol and Lipoprotein(a) Lowering in Response to PCSK9 Inhibition With Evolocumab. J Am Heart Assoc. 2019 Feb 19;8(4):e010932. doi: 10.1161/JAHA.118.010932.
Background: PubMed 30120772Stroes E, Robinson JG, Raal FJ, Dufour R, Sullivan D, Kassahun H, Ma Y, Wasserman SM, Koren MJ. Consistent LDL-C response with evolocumab among patient subgroups in PROFICIO: A pooled analysis of 3146 patients from phase 3 studies. Clin Cardiol. 2018 Oct;41(10):1328-1335. doi: 10.1002/clc.23049. Epub 2018 Oct 21.
Background: PubMed 32114889Toth PP, Jones SR, Monsalvo ML, Elliott-Davey M, Lopez JAG, Banach M. Effect of Evolocumab on Non-High-Density Lipoprotein Cholesterol, Apolipoprotein B, and Lipoprotein(a): A Pooled Analysis of Phase 2 and Phase 3 Studies. J Am Heart Assoc. 2020 Mar 3;9(5):e014129. doi: 10.1161/JAHA.119.014129. Epub 2020 Mar 2.
Background: PubMed 32564340Koren MJ, Jones PH, Robinson JG, Sullivan D, Cho L, Hucko T, Lopez JAG, Fleishman AN, Somaratne R, Stroes E. A Comparison of Ezetimibe and Evolocumab for Atherogenic Lipid Reduction in Four Patient Populations: A Pooled Efficacy and Safety Analysis of Three Phase 3 Studies. Cardiol Ther. 2020 Dec;9(2):447-465. doi: 10.1007/s40119-020-00181-8. Epub 2020 Jun 20.
AmgenTrials clinical trials websiteLink provided by the sponsor.

Related trials for Hyperlipidemia

Not yet recruiting
Plasma Lipids-Dependent Vitamin E Metabolism During Dynamic Hyperlipidemia
Lipid Metabolism Disorders
Active, not recruiting
Developing a Learning COmmunity to Increase eNgagemeNt and Enrollment in Cardiovascular Clinical Trials (CONNECT)
Cardiovascular Diseases, Hypertension
Active, not recruitingPhase 3
A Study of Inclisiran to Prevent Cardiovascular Events in High-risk Primary Prevention Patients.
Primary Prevention of Atherosclerotic Cardiovascular Disease
RecruitingObservational study
Causes and Natural History of Dyslipidemias
Hypercholesterolemia, Atherosclerosis
Active, not recruitingObservational study
Early Detection of Familial Hypercholesterolaemia in Pre-school Children ( CzeCH-IT)
Familial Hypercholesterolaemia

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

MD study director

Amgen

58 sites in 14 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Evolocumab and Ezetimibe in people with Hyperlipidemia, run by Amgen at 58 sites in 14 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 58 sites in United States, Australia, United Kingdom, Belgium, Canada and 9 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Dec 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percent Change From Baseline in LDL-C at Week 12 (time frame: Baseline and Week 12). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01763905, which also lists 11 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jul 2020.